Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 131, P. 106328 - 106328
Published: Dec. 17, 2022
Language: Английский
Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)
Published: Sept. 25, 2023
Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities contributes to the formation of tumor microenvironment (TME). Importantly, increased expression activity are strongly associated with unfavorable clinical outcomes metastatic characteristics numerous tumors. vitro vivo studies have demonstrated that modulating by application inhibitors alone or combination treatment regimens could be effective for therapy. Based on these findings, several agents targeting been exploited diverse preclinical models. This article briefly describes structure function FAK, well research progress therapies. We also discuss challenges future directions regarding anti-FAK
Language: Английский
Citations
59
Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 12, 2024
Focal adhesion kinase (FAK) is a non-receptor tyrosine that exhibits high expression in various tumors and associated with poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, angiogenesis via both kinase-dependent kinase-independent pathways. Moreover, crucial for sustaining the microenvironment. The inhibition of impedes tumorigenesis, drug resistance cancer. Therefore, developing targeted inhibitors against presents promising therapeutic strategy. To date, numerous inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, APG-2449, have been developed, which demonstrated positive anti-tumor effects preclinical studies are undergoing clinical trials several types tumors. many novel currently to advance therapy aberrantly activated FAK. benefits degraders, especially terms their scaffold function, increasingly evident, holding potential future exploration breakthroughs. This review aims clarify FAK's role cancer, offering comprehensive overview current status prospects FAK-targeted combination approaches. goal provide valuable insights advancing anti-cancer treatment strategies.
Language: Английский
Citations
25
Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)
Published: Jan. 13, 2025
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.
Language: Английский
Citations
16
Gene, Journal Year: 2025, Volume and Issue: 941, P. 149229 - 149229
Published: Jan. 10, 2025
Language: Английский
Citations
4
Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1824 - 1824
Published: April 4, 2022
Cervical cancer is the fourth most frequent malignancy in women. Apigenin a natural plant-derived flavonoid present common fruit, vegetables, and herbs, has been found to possess antioxidant anti-inflammatory properties as health-promoting agent. It also exhibits important anticancer effects various cancers, but its are not widely accepted by clinical practitioners. The study investigated molecular mechanisms of apigenin cervical vitro vivo. HeLa C33A cells were treated with different concentrations apigenin. on cell viability, cycle distribution, migration potential, phosphorylation PI3K/AKT, integrin β1-FAK signaling pathway, epithelial-to-mesenchymal transition (EMT)-related protein levels investigated. Mechanisms identified from further validated tumor xenograft mouse model. effectively inhibited growth tumors mice. Furthermore, down-regulated FAK (FAK, paxillin, β1) PI3K/AKT (PI3K, AKT, mTOR), inactivated or activated targets, such Bcl-2, Bax, p21cip1, CDK1, CDC25c, cyclin B1, fibronectin, N-cadherin, vimentin, laminin, E-cadherin, promoted mitochondrial-mediated apoptosis, induced G2/M-phase arrest, reduced EMT inhibit migration, producing cancer. Thus, may act chemotherapeutic agent for treatment.
Language: Английский
Citations
40
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: Aug. 21, 2023
Part of the broader glycosphingolipid family, gangliosides are composed a ceramide bound to sialic acid-containing glycan chain, and locate at plasma membrane. Gangliosides produced through sequential steps glycosylation sialylation. This diversity composition is reflected in differences expression patterns functions various gangliosides. Ganglioside GD2 designates different subspecies following basic structure containing three carbohydrate residues two acids. expression, usually restrained limited tissues, frequently altered neuroectoderm-derived cancers. While evident interest, its glycolipid nature has rendered research challenging. Physiological been linked developmental processes. Passing this stage, varying levels GD2, physiologically expressed mainly central nervous system, affect formation membrane microdomains involved surface receptor signaling. Overexpressed cancer, shown enhance cell survival invasion. Furthermore, binding antibodies leads immune-independent death mechanisms. In addition, contributes T-cell dysfunction, as an immune checkpoint. Given cancer-associated functions, source interest for immunotherapy. As potential biomarker, methods being developed quantify from patients’ samples. therapeutic strategies tested. Based on initial success with antibodies, derivates such bispecific immunocytokines have developed, engaging patient system. Cytotoxic effectors or payloads may be redirected based anti-GD2 antibodies. Finally, vaccines can used mount response patients. We review here pertinent biological information which use optimizing current immunotherapeutic strategies.
Language: Английский
Citations
27
IUBMB Life, Journal Year: 2024, Volume and Issue: 76(7), P. 383 - 396
Published: Jan. 17, 2024
Abstract Wnt signaling is essential for embryonic development, influencing processes such as axis formation, cell proliferation and differentiation, fate decisions, axon guidance. It also plays a role in maintaining tissue homeostasis adult organisms. The loss of normal polarity adhesion caused by activation fundamental step tumor progression metastasis. Activating the canonical pathway driving force many human cancers, especially colorectal, hepatocellular, mammary carcinomas. causes stabilization nuclear transport newly synthesized transcriptional regulator β‐catenin. generally accepted view that effects growth factors are transcription β‐catenin target genes. Here, we review recent findings indicate other cellular physiological activities, macropinocytosis, endosome trafficking, protein stability, focal adhesions, lysosomal activity. Some these regulatory responses occur within minutes do not require new synthesis, indicating there much more to beyond well‐established main conclusion emerges from studies basal conditions, activity key kinase GSK3, which inhibited activation, normally represses actin machinery orchestrates macropinocytosis with implications cancer. These contributions expand our understanding multifaceted roles processes, cancer, providing insights into potential therapeutic targets strategies.
Language: Английский
Citations
10
European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117328 - 117328
Published: Feb. 2, 2025
Language: Английский
Citations
1
Annals of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 27, 2025
Language: Английский
Citations
1
Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)
Published: March 5, 2025
The tumour microenvironment is the "hotbed" of cells, providing abundant extracellular support for growth and metastasis. However, not static constantly remodelled by a variety cellular components, including through mechanical, biological chemical means to promote Focal adhesion plays an important role in cell-extracellular matrix adhesion. An in-depth exploration focal metastasis, especially their contribution at biomechanical level, direction current research. In this review, we first summarize assembly adhesions explore kinetics cells. Then, describe detail various stages its key functions cell migration, invasion, remodelling. Finally, anti-tumour strategies targeting progress development some inhibitors against proteins. paper, time that play positive feedback pro-tumour metastatic remodelling summarizing five processes multidimensional way. It beneficial researchers have deeper understanding behaviour metastasis potential as therapeutic target, new ideas prevention treatment metastases.
Language: Английский
Citations
1